Water → HCID 58319584, compound

HRID 929896Notes

Reaction equation

HRID 929896 reaction equation
[C:1]([O:5][C:6]([C@:8]1([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:13][C@H:12]([OH:14])[C@@H:11]2[C@H:9]1[C@H:10]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:30]1([CH3:40])[CH:35]=[CH:34][C:33]([S:36](Cl)(=[O:38])=[O:37])=[CH:32][CH:31]=1.S([O-])(O)(=O)=O.[K+].O>CN(C)C1C=CN=CC=1.ClCCl.C(N(CC)CC)C>[C:1]([O:5][C:6]([C@:8]1([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:13][C@H:12]([O:14][S:36]([C:33]2[CH:34]=[CH:35][C:30]([CH3:40])=[CH:31][CH:32]=2)(=[O:38])=[O:37])[C@@H:11]2[C@H:9]1[C@H:10]2[C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 962WaterHCID 73974-Toluenesulfonyl chlorideHCID 516920Potassium bisulfateHCID 59712892ditert-butyl(1S,2S,4S,5R,6R)-2-(tert-butoxycarbonylamino)-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylate

Product 1

HCID 58319584HCID 58319584, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 8471TriethylamineCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Charge a 2-necked round bottom flask under nitrogen atmosphere with ditert-butyl(1S,2S,4S,5R,6R)-2-(tert-butoxycarbonylamino)-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylate (20.7 g, 0.5 mol, see WO03/104217/A2 for synthesis details), 4-dimethylaminopyridine (10.4 g, 0.85 mol), triethylamine (6.98 mL, 0.5 mmol) and p-toluenesulfonyl chloride (10.6 g, 0.55 mol) in dichloromethane (200 mL), and stir the mixture at room temperature overnight. Add 1N solution of potassium hydrogen sulfate (200 mL), water (100 mL) and extract the organic layer. Wash with water (200 mL), brine (200 mL), dry over magnesium sulfate, filter and evaporate to dryness. Add tetrahydrofuran (30 mL) then heptanes (90 mL). Heat the mixture at 60° C. and slowly add more heptanes (200 mL). Cool the mixture to room temperature. Filter the solid and dry under reduced pressure to yield the title compound as a white solid (24.6 g, 87%). MS (m/z): 590 (M+23).

Workup

  1. extractionextract the organic layer
  2. washWash with water (200 mL), brine (200 mL)
  3. dry with materialdry over magnesium sulfate
  4. filtrationfilter
  5. customevaporate to dryness
  6. temperatureHeat the mixture at 60° C.
  7. additionslowly add more heptanes (200 mL)
  8. temperatureCool the mixture to room temperature
  9. filtrationFilter the solid
  10. customdry under reduced pressure

Sources & evidence

ORD record
ord-06942330eb844b6f89b4a355fd33113c
Source dataset
uspto-grants-2016_03
Patent number
US09296710B2

Reaction notes

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